Oral and pharyngeal cancer incidence in Puerto Rican males is notably higher than among white males living on the U.S. mainland. Oral epithelial dysplasia (OED) is a histopathological diagnosis characterized bj cellular changes and maturational disturbances. A diagnosis of OED is significant in that it is associated with an elevated risk of transformation to oral cancer. Few epidemiologic studies have investigated environmental risk factors for OED, and no such studies have been carried out in an Hispanic population. The primary aim oi this study is to estimate the association between OED and the use of smoking tobacco and alcoholic beverages in an Hispanic population living in Puerto Rico. On an exploratory basis the proposed investigation will (a) examine for the presence of a dose-response relationship as regards OED and both smoking tobacco and alcohol use, (b) test for a synergistic relationship between alcohol and smoking with regard to OED, (c) evaluate smokeless tobacco, mouthwash use and dentures as OED risk factors, (d) evaluate dietary habits as risklprotective factors for OED, and (e) examine whether polymorphisms in genes that code for enzymes active in the carcinogen activation and detoxification pathways are associated with OED. OED cases (aged 20-79) will be identified by reviewing biopsy reports generated by pathology laboratories on the Island. The control series, frequency matched 1 : 1 to cases on age, gender, and geographic region, will consist of persons diagnosed with an irritation fibroma via the same pathology laboratories. Environmental risk factor data will be obtained using a structured questionnaire. Oral cells will be obtained for DNA extraction and used in studies of genetic polymorphisms while paraffin-embedded tissue from cases and controls will be available for immunohistochemical and molecular analyses. Adjusted odds ratios will be obtained from logistic regression models. Information obtained from this study will further our understanding of the etiology of OED, provide possible explanations for the high rates of oral and pharyngeal cancer in Puerto Rico, and suggest opportunities for the primary prevention of OED and oral cancer.